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EP1139860B1 - System zur messung eines bioanalyts wie laktat - Google Patents

System zur messung eines bioanalyts wie laktat Download PDF

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Publication number
EP1139860B1
EP1139860B1 EP99964283A EP99964283A EP1139860B1 EP 1139860 B1 EP1139860 B1 EP 1139860B1 EP 99964283 A EP99964283 A EP 99964283A EP 99964283 A EP99964283 A EP 99964283A EP 1139860 B1 EP1139860 B1 EP 1139860B1
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EP
European Patent Office
Prior art keywords
adapter
passage
catheter
conduit
sensor assembly
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP99964283A
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English (en)
French (fr)
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EP1139860A1 (de
Inventor
James L. Say
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Pepex Biomedical Inc
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Pepex Biomedical Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1495—Calibrating or testing of in-vivo probes

Definitions

  • This invention relates generally to systems and methods for measuring bioanalytes. More particularly, the present invention relates to systems and methods for measuring lactate.
  • Clinical laboratories offer a wide range of automated systems for high-volume testing and analytical support in a well controlled, high quality environment. However, clinical laboratories can not provide the immediate results needed to properly treat trauma and multi organ dysfunction/failure patients.
  • POC diagnostic test systems include electrochemical biosensors, optical fluorescence sensors, paramagnetic particles for coagulation test systems, and micromachined devices for both chemical and immunochemical testing. These technologies have allowed multi-analyte chemistry panels to be performed rapidly and have addressed previous obstacles such as calibration of test devices.
  • POC tests can be classified as: 1) in vitro, which is performed at the bedside; 2) ex vivo or para vivo, which is performed at wrist-side; and 3) in vivo, which is performed inside the patient.
  • POC tests offer indirect cost efficiencies and savings such as reduced labor costs, decreased blood identification and transport errors, and reduced patient complications.
  • In vitro or bedside POC devices are used typically in several departments of the hospital including intensive care units; operating rooms; emergency departments (ER); interventional departments; general patient care departments; and outpatient surgery and ambulatory care units.
  • In vitro POC diagnostic tests offer a wide range of diagnostic tests, similar to the clinical laboratory.
  • In vitro POC diagnostic test systems typically are not connected on-line to the patient and require an operator for blood sampling.
  • Key categories of diagnostic test in the POC diagnostic market include arterial blood gases, blood chemistries, blood glucose, coagulation, drugs-of abuse testing, hemoglobin, hermatocrit, infectious diseases, and therapeutic drug monitoring.
  • Other categories include cancer marker, cardiac markers, cholesterol detection, immunodiagnostics, infectious disease detection, lactate, and thrombolytic monitoring.
  • PCT WO 94/21163 discloses an exemplary in vivo POC system that teaches the use of a tonometric catheter to monitor or maintain the adequacy of tissue oxygenation through the measurement of acid-balance in specific tissues. It also discloses several sensor assemblies as well as multi-passage tubing defining at least two flow lines.
  • Ex vivo POC diagnostics use external sensors for on-line real-time testing with little to no blood loss. Typically, sampled blood flows through a closed system to minimize blood contact. Ex vivo POC systems minimize problems associated with in vivo sensors, including clotting, inaccuracy, calibration drift, and an inability to recalibrate once in the patient.
  • Optical Sensors, Inc. of Minneapolis, Minnesota currently markets ex vivo blood gas analyzers which utilize a hand operated syringe system.
  • VIA Medical Corporation of San Diego, California markets ex vivo blood glucose analyzers which utilize a relatively large volume, automated sampling and analysis system.
  • United States Patent No. 5,505,828 discloses an exemplary ex vivo POC system with an intravenous (IV) port, in which a hollow needle/catheter combination is inserted into a blood vessel of the patient.
  • IV intravenous
  • Ex vivo and in vivo POC diagnostics can reduce quality control and information integration errors that occur with clinical or in vitro POC tests.
  • Quality control errors are commonly due to operator errors, not instrument errors or device failures. Exemplary errors include inappropriate specimen volume, inaccurale calibration, use of deteriorated test strips, inadequate validation, insufficient instrument maintenance, bad timing of the test procedure, and use of the wrong materials.
  • Clinical information system integration allows test data collected at the bedside to be put directly into the patient record. This improves the efficiency of the patient management process, allowing the integration of the laboratory's information system and clinical information systems, providing a "seamless" flow of all types of patient information.
  • One aspect of the present invention relates to a sensor assembly including a catheter having a catheter sheath adapted for insertion in a patient, and a catheter hub connected to the catheter sheath. Therefore the present invention provides:
  • a sensor assembly (20) comprising a catheter (22) including a catheter sheath (24) adapted for insertion in a patient, a pump (34), a sensor (30) and a container (32) for holding a calibration fluid, the calibration fluid including a calibrant adapted for use in calibrating the sensor (30), whereby the sensor assembly (20) further comprises a catheter hub (26) connected to the catheter sheath (24); an adapter (28) connected to the catheter hub (26), the adapter including the first and second ports (100; 102); the adapter (28) defining first and second separate passages (54; 56), the first passage (54) extending from the first port (100) to an interior region (50) of the catheter sheath (24), and the second passage (56) extending from the second port (102) to an interior region of the catheter hub (26); two flow lines, the first flow line (38) extending between the adapter (28) and the pump (34), and the first flow line (38) being connected to the first port (100) of the adapter (28) and the second flow line (40)
  • a second aspect of the invention is an adapter for use with a catheter as generally described in claim 17 and with respect to preferred embodiments in claims 18 to 22. catheter hub.
  • the adapter includes first and second ports.
  • a first flow line extends between the first port of the adapter and a pump.
  • a sensor is positioned along the first flow line.
  • a second flow line extends from the second port of the adapter to a container for holding a calibration fluid.
  • the calibration fluid includes a calibrant adapted for use in calibrating the sensor.
  • the adapter of the sensor assembly defines first and second separate passages. The first passage extends from the first port to an interior region of the catheter sheath. The second passage extends from the second port to an interior region of the catheter hub.
  • a sensor assembly including a catheter having a catheter sheath adapted for insertion in a patient.
  • the assembly also includes a first structure defining a first flow passage that terminates within an interior region of the catheter sheath, and a second structure defining a second flow passage separate from the first flow passage that also terminates within the interior region of the catheter sheath.
  • a sensor is positioned in fluid communication with the first flow passage, and a source of calibration fluid is in fluid communication with the second flow passage.
  • the assembly further includes a pump in fluid communication with the first flow passage.
  • a further aspect of the present invention relates to a method of operating a sensor assembly as described above.
  • the method includes inserting the catheter sheath into the patient.
  • the method also includes conveying calibration fluid through the second flow passage from the source of calibration fluid into the interior region of the catheter sheath.
  • the method further includes calibrating the sensor by pumping the calibration fluid from the interior region of the catheter sheath through the first flow passage, and conveying the calibration fluid past the sensor.
  • a sample fluid is drawn from the patient by terminating the conveyance of calibration fluid to the interior region of the catheter sheath, and pumping a sample fluid from the interior region of the catheter sheath through the first flow line to the sensor. Finally, the sample fluid is sensed by the sensor.
  • Still another aspect of the present invention relates to an adapter for use with a catheter including a catheter sheath connected to a catheter hub.
  • the catheter sheath is adapted for insertion in a patient.
  • the adapter includes an adapter body defining first and second ports adapted for connection to medical tubing.
  • the adapter also includes a connecting member adapted to fasten the adapter body to the hub.
  • the adapter further includes a conduit extending from the first port through the adapter body.
  • the conduit includes an end portion that projects outward from the adapter body. The end portion is arranged and configured to fit within an interior region of the catheter sheath when the adapter body is connected to the catheter hub.
  • the adapter additionally includes structure defining a passage separate from the conduit that extends from the second port through the adapter body to the catheter sheath.
  • An aspect of the present invention relates to systems and methods for providing on-line monitoring/measurement of bioanalytes in a patient.
  • One particular aspect of the present invention relates to systems and methods for providing on-line measurement of lactate concentrations in a patient.
  • Lactate is a small molecule that is produced by all tissues and organs of a patient's body that are in "distress". Wherever in the patient's body the demands for oxygen exceed the supply, then a state of low perfusion exists and lactate is produced. For example, lactate is produced if a patient is bleeding, if a patient's heart is failing, if a person's limb is in danger of being lost, or if a person is not getting enough oxygen to breathe. Thus many life and limb threatening clinical states produce elevated blood lactate levels, even in the face of adequate oxygen delivery to the patient. It is a matter of oxygen supply and metabolic demand.
  • lactate is inversely proportional to the vital cellular energy stores of adenosine triphosphate and is produced within six seconds of inadequate perfusion or cellular injury. It is thus an ideal biochemical monitor of cellular viability at the tissue level, and of patient viability at the systemic level.
  • blood lactate is the best indicator of the degree of shock (superior to blood pressure, heart rate, urine output, base deficit, blood gas and Swan-Ganz data) and is proportional to the shed blood volume. Blood lactate levels correlate with a trauma patient's chances of survival. Therapy that fails to control a patient's increasing lactate levels must be modified or additional diagnoses quickly sought.
  • FIG. 1 schematically shows a sensor assembly 20 for providing on-line monitoring/measurement of bioanalytes such as lactate in a patient.
  • the sensor assembly 20 includes a catheter 22 (e.g., a peripheral catheter) including a catheter sheath 24 connected to a catheter hub 26 (i.e., a luer fitting).
  • the sensor assembly 20 also includes an adapter 28 connected to the catheter hub 26, a sensor 30, a source of calibration fluid 32, a pump 34 (e.g., a syringe driven by a syringe driver) and a waste container 36 (e.g., a waste bag).
  • a first flow line 38 connects the adapter 28 to the pump 34.
  • the sensor 30 is positioned along the first flow line 38.
  • a second flow line 40 interconnects the adapter 28 and the source of calibration fluid 32.
  • a third flow line 42 extends between the first flow line 38 and the waste container 36.
  • a controller 144 e.g., a micro-controller, a mechanical controller, a software driven controller, a hardware driven controller, a firmware driven controller, etc. preferably interfaces with both the sensor 30 and the pump 34.
  • the first flow line 38 provides fluid communication between the adapter 28 and the pump 34.
  • the first flow line 38 functions to convey fluid from the adapter 28 through the sensor 30.
  • a first check valve 44 is positioned along the first flow line 38 at a location between the sensor 30 and the pump 34.
  • the first check valve 44 allows fluid to flow through the first flow line 38 in a direction from the adapter 28 toward the pump 34, but prevents or blocks fluid flow through the first flow line 38 in a direction from the pump 34 toward the adapter 28.
  • the third flow line 42 branches off from the first flow line 38 at a location positioned between the first check valve 44 and the pump 34.
  • a second check valve 46 is positioned along the third flow line 42. The second check valve 46 allows fluid flow through the third flow line 42 in a direction toward the waste container 36, but blocks or prevents fluid flow through the third flow line 42 in a direction away from the waste container 36.
  • the second flow line 40 functions to convey calibration fluid from the source of calibration fluid 32 to the adapter 28.
  • a valve structure such as a pinch valve 48 is used to selectively open and close the second flow line 40.
  • the second flow line 40 is open, calibration fluid flows through the second flow line 40 to the adapter 28.
  • the second flow line 40 is closed, the flow of calibration fluid to the adapter 28 is stopped.
  • the adapter 28 and the catheter 22 of the sensor assembly 20 preferably cooperate to provide two separate passages that respectively connect the first and second flow lines 38 and 40 to a fluid exchange region 55.
  • the fluid exchange region 55 is located within an interior region 50 of the catheter sheath 34 adjacent to a distal tip 57 of the catheter sheath 24.
  • the adapter 28 defines a first passage 54 that extends from the first flow line 38, through the catheter hub 26, to the interior region 50 of the catheter sheath 24.
  • the first passage 54 terminates within the interior volume 50 of the sheath 24 at the fluid exchange region 55.
  • the first passage 54 has a termination location 59 (i.e., the location of the tip of the conduit defining the first passage 54) that is spaced a length L from the distal tip 57 of the catheter sheath 24.
  • the length L does not exceed 1 centimeter.
  • the length L does not exceed 5 millimeters.
  • the length L does not exceed 2 millimeters.
  • the length L does not exceed 1 millimeter.
  • the adapter 28 and the catheter 22 cooperate to define a second passage 56 that extends from the second flow line 40 to the fluid exchange region 55.
  • the second passage 56 includes a first portion 61 defined through the adapter 28, a second portion 63 defined through the catheter hub 26, and a third portion 65 defined through the catheter sheath 24.
  • the portions 61, 63 and 65 are all in fluid communication with one another.
  • the first portion 61 extends through the adapter 28 from the second flow line 40 to the second portion 63
  • the second portion extends through the catheter hub 26 from the first portion 61 to the third portion 65
  • the third portion 65 extends through the catheter sheath 24 from the second portion 63 to the fluid exchange region 55.
  • the second and third portions 63 and 65 of the second passage 56 concentrically surround the first passage 54.
  • Figure 2 provides an exploded illustration of the various components of an adapter 28' suitable for use with the sensor assembly 20.
  • the adapter 28' includes an insertion portion 58, a connecting member or collar 60, a fluid manifold 62, a dual tube receiver 64, a draw tube or conduit 66 and a tubing step-down connector 68 connected to the conduit 66.
  • the insertion portion 58 of the adapter 28' is generally cylindrical and includes a first end 70 positioned opposite from a second end 72.
  • a radial shoulder 74 projects outward from the insertion portion 58 at a location intermediate the first and second ends 70 and 72.
  • the frustral conical shaped portion has a minor diameter located directly at the first end 70 of the insertion portion 58, and a major diameter located adjacent to the radial shoulder 74.
  • the frustral conical shaped portion 76 has an exterior taper that compliments a corresponding taper 77 of an interior region 77 of the catheter hub 26 such that the frustral conical shaped portion 76 is sized and shaped to be received within the catheter hub 26.
  • the insertion portion 58 defines an axial bore 78 that extends completely through the insertion portion 58 between the first and second ends 70 and 72.
  • the axial bore 78 has an enlarged diameter portion 79 positioned adjacent the second end 72 of the insertion portion 58, and a reduced diameter portion 80 that extends through the first end 70 of the insertion portion 58.
  • a tapered transition region 82 is defined between the enlarged diameter portion 79 and the reduced diameter portion 80.
  • the collar 60 of the adapter 28' is preferably generally cylindrical and defines a generally cylindrical inner chamber 84 sized to receive the catheter hub 26.
  • the collar 60 preferably defines a plurality of interior threads positioned within the inner chamber 84.
  • the interior threads are preferably configured such that the collar 60 can be threaded on corresponding exterior threads formed on the outer surface of the catheter hub 26.
  • the collar 60 also includes a radial end wall 86 defining a central opening 88 sized for receiving the second end 72 of the insertion portion 58.
  • the fluid manifold 62 of the adapter 28' includes a main portion 90 and an extension 92 that projects axially outward from the main portion 90.
  • the extension 92 is generally cylindrical and includes an inner axial opening 94 sized for receiving the second end 72 of the insertion portion 58.
  • the main portion 90 defines a recess 96.
  • the main body 90 also includes a circumferential shoulder 98 that projects radially into the recess 96.
  • the dual tube receiver 64 of the adapter 28' defines first and second ports 100 and 102.
  • the first port 100 is sized for receiving the step-down connector 68 connected to the conduit 66.
  • the step down connector 68 is sized to receive an end of the first flow line 38.
  • the second port 102 is sized to receive an end of the second flow line 40.
  • the dual tube receiver 64 includes a reduced diameter portion 104 sized to fit within the recess 96 of the fluid manifold 62.
  • Figures 3 and 4 show the adapter 28' as assembled.
  • the second end 72 of the insertion portion 58 is inserted within the extension 92 of the fluid manifold 62.
  • the reduced diameter portion 104 of the dual tube receiver 64 is inserted within the recess 96 of the fluid manifold 62.
  • the insertion portion 58, the fluid manifold 62 and the dual tube receiver 64 are preferably bonded together to form a main adapter body.
  • the collar 60 is rotatably mounted between the radial shoulder 74 of the insertion portion 58 and the extension 92 of the fluid manifold 62.
  • the step-down connector 68 is mounted within the first port 100 of the dual tube receiver 64, and the first flow line 38 is press fit within the step-down connector 68.
  • the second flow line 40 is press fit within the second port 102.
  • the conduit 66 extends axially from the step down connector 68 through an opening 106 defined by the dual tube receiver 64 into the insertion portion 58. Within the insertion portion 58, the conduit 66 extends axially through the axial bore 78. An end portion 108 of the conduit projects axially outward from the first end 70 of the insertion portion 58.
  • the conduit 66 extends through the reduced diameter portion 80 of the insertion portion 58.
  • the reduced diameter portion 80 has a diameter of .030 inch (0,762 mm), and the conduit 66 has an outer diameter of .016 inch (0.4064mm).
  • Such a variation in diameters provides a relatively loose fit between the conduit 66 and the reduced diameter portion 80.
  • the relatively loose fit between the conduit 66 and the reduced diameter portion 80 allows fluid traveling through the axial bore 78 to exit the insertion portion 58 through the reduced diameter portion 80. Fluid exiting the axial bore 78 circumferentially/concentrically surrounds the conduit 66 as it travels through the reduced diameter portion 80.
  • the adapter 28' defines a flow passage that extends from the second flow line 40 axially through an opening 110 defined by the dual tube receiver 64.
  • the passage then extends along a radial passage portion 112 defined between the fluid manifold 62 and the dual tube receiver 64.
  • the reduced diameter portion 104 of the dual tube receiver 64 abuts against the circumferential shoulder 98 of the fluid manifold 62 such that an axial spacing S of the radial passage portion 112 is maintained.
  • the passage extends in an axial direction along the axial bore 78 of the insertion portion 58.
  • the insertion portion 58 fits within the catheter hub 26 and the collar 60 is threaded on the exterior of the catheter hub 26.
  • the first end 70 of the insertion portion 58 projects into the interior cavity 77 of the catheter hub 26, and the end portion 108 of the conduit 66 projects or extends into the interior of the catheter sheath 24.
  • the tip of the conduit 66 is preferably positioned at a fluid exchange region 55' located adjacent the distal tip 57 of the catheter sheath 24.
  • Fluid communication is provided between the axial bore 78 of the adapter 28 and the interior cavity 77 of the catheter hub 26 via the reduced diameter portion 80 of the axial bore 78 (i.e., fluid in the axial bore 78 can enter the catheter hub 26 by flowing between the conduit 66 and the region of the insertion portion 58 that defines the reduced diameter portion 80.) Fluid communication is also provided between the interior cavity 77 of the hub 26 and the interior of the catheter sheath 24.
  • the hub defines an end opening 81 that is sufficiently larger than the conduit 66 to allow fluid to freely flow between the interior cavity 77 of the hub 26 and an annular passage 79 that surrounds the conduit 66 within the sheath 24.
  • the annular passage 79 is defined between the conduit 66 and the catheter sheath 24 and is configured to convey fluid from the interior cavity 77 of the hub 26 to the fluid exchange region 55'.
  • the sensor 30' includes a housing 113 having a top piece 114 that is fastened to a bottom piece 116 by conventional techniques such as fasteners (e.g., screws).
  • a substrate 118 is positioned between the top and bottom pieces 114 and 116.
  • the substrate 118 includes a reference electrode 120, a working electrode 122, and a counter electrode 124.
  • the electrodes are coupled to a connector 126 by conductive traces 128.
  • the connector 126 is preferably connected to the controller 144 of the sensor assembly 20.
  • An adhesive layer 130 is positioned between the circuit board 118 and the top piece 114.
  • the adhesive layer 130 defines a slot 132 that extends across the electrodes 120, 122 and 124. In this manner, the slot 132 functions to define a test chamber 134 within the housing 113 of the sensor 30'.
  • Fluid flowing through the first flow line 38 flows in a direction D through the sensor housing 113.
  • a flow path through the sensor housing is at least partially defined by a resilient (e.g., urethane) member 136 that is press fit within the top piece 114.
  • the resilient member 136 has ends defining notches 138 that each provide a transverse (i.e., upright) flow path within the sensor housing 113.
  • flow within the first flow line 38 enters the sensor housing through a first port 140, flows downward along one of the notches 138 to the test chamber 134, flows along the test chamber 134 across the electrodes 120, 122 and 124, flows upward along the other notch 138, and exits the sensor housing through a second port 142.
  • the sensor 30' is preferably a wired enzyme sensor for detecting or measuring bioanalytes.
  • Illustrative wired enzyme sensors are described in United States Patent Nos. 5,264,105; 5,356,786; 5,262,035; and 5,320,725.
  • working and counter electrodes 120,122 and 124 are formed as separate conductive lines or traces on the substrate 118. At least portions of the reference, working and counter electrodes 120, 122 and 124 are positioned along the test chamber 134 of the sensor 30' when the sensor 30' is assembled as shown in Figure 6.
  • the working electrode 122 is the electrode at which an analyte such as lactate or glucose is electrooxidized or etectroreduced. Current is passed between the working electrode 122 and the counter electrode 124. The potential of the working electrode 122 is monitored relative to the reference electrode 124. Since essentially no current is passed through the reference electrode 120, its potential will remain constant and equal to its open-circuit value. This system is called a three-electrode system.
  • the counter electrode 124 can be used as a working electrode too, and the reference electrode 120 will also act a counter electrode. Since the current is small, the passage of the low current through the reference electrode 120 will not effect the potential of the reference elcetrode 120.
  • the reference, working and counter electrodes 120,122 and 124 are positioned within the test chamber 134.
  • the chamber 134 is configured so that when a sample is provided in the chamber 134, the sample is in fluid contact with the reference, working, and counter electrodes 120, 122 and 124. This allows electrical current to flow between the electrodes 120, 122 and 124 to effect the electrolysis (electrooxidation or electroreduction) of the analyte.
  • the working/counter electrodes 122 and 124 may be formed by any conductive material.
  • Exemplary conductive materials include carbon, gold, platinum, graphite, palladium and tin oxide.
  • the working electrodes 122 preferably have test surfaces that are covered with a sensing layer.
  • the sensing layer preferably includes a redox compound or mediator.
  • the term redox compound is used herein to mean a compound that can be oxidized and reduced.
  • Exemplary redox compounds include transition metal complexes with organic ligands.
  • Preferred redox compounds/mediators are osmium transition metal complexes with one or more ligands having a nitrogen containing heterocycle such as 2, 2'-bipyridine.
  • the sensing layer can also include a redox enzyme.
  • a redox enzyme is an enzyme that catalyzes an oxidation or reduction of an analyte.
  • a glucose oxidase or glucose dehydrogenase can be used when the analyte is glucose.
  • a lactate oxidase or lactate dehydrogenase fills this role when the analyte is lactate.
  • these enzymes catalyze the electrolysis of an analyte by transferring electrons between the analyte and the electrode via the redox compound.
  • the reference electrode 120 can be constructed in a manner similar to the working/counter electrodes 122 and 124. Suitable materials for the reference electrode 120 include Ag/AgCl printed on a non-conducting base material or silver chloride on a silver metal base.
  • a previously determined potential is applied across the reference and working electrodes 120 and 122.
  • an electrical current will flow between the working electrode 122, counter electrode 124 and reference electrode 120.
  • the current is a result of the electrolysis of the analyte in the sample fluid.
  • This electrochemical reaction occurs via the redox compound and the optional redox enzyme.
  • a temperature probe can be formed as a line on the substrate 118.
  • temperature probes can be located elsewhere within the chamber 134, outside the test chamber 134, or at alternative locations along the flow path 38. The temperature probes preferably interface with the control unit 144.
  • the catheter 22 of the sensor assembly 20 is a conventional peripheral catheter. Of course, other types of catheters can also be utilized for withdrawing test fluids from a patient.
  • the first, second and third flow lines 36, 38 and 40 of the sensor assembly 20 are preferably formed by conventional medical tubing.
  • the source of calibration fluid 32 of the sensor assembly 20 can be a conventional intravenous (IV) bag that feeds calibration fluid to the adapter 28 via gravity through the second flow line 38.
  • IV intravenous
  • a preferred calibration fluid includes a predetermined concentration of a calibrant such as lactate for lactate sensors, or glucose for glucose sensors.
  • the calibration fluid can include a variety of other components in addition to a calibrant.
  • an anticoagulant such as sodium citrate can be used.
  • a preferred calibration fluid comprises a solution of sodium citrate, saline and lactate.
  • lactate is only used as a calibrant if a lactate sensor is being used in the system.
  • Other types of calibrants that may be used in the system include glucose, potassium, sodium, calcium and ringers lactate.
  • the catheter 22 is inserted at an appropriate site (e.g., the patient's lower arm).
  • the source of calibration fluid 32 and the waste container 36 are then placed at the appropriate locations.
  • the source of calibration fluid 32 comprises an intravenous (IV) bag
  • IV intravenous
  • the waste container 36 comprises a conventional waste bag
  • such bag is preferably hung at a level below the catheter insertion site.
  • the pinch valve 48 of the second flow line 40 is opened thus beginning an infusion of the calibrant into the patient.
  • the calibration fluid flows from the source of calibration fluid 32 to the adapter 28. From the adapter 28, the calibration fluid flows through the second passage 56 into the fluid exchange region 55 defined within the catheter sheath 24. From the fluid exchange region 55, the calibration fluid infuses into the patient.
  • a calibration phase is initiated in which the pump 34 (e.g., a syringe drawn by a conventional syringe driver) generates a lower pressure gradient that causes the calibration fluid within the fluid exchange region 55 of the catheter sheath 24 to be drawn into the first passage 54 (as shown in Figure 8). From first passage 54, the calibration fluid flows into the first flow line 38 toward the sensor 30.
  • the flow of calibration fluid toward the patient is regulated so as to always be in a ratio of at least two times the draw rate of the pump 34.
  • the flow rate through the first flow line 38 toward the sensor 30 is about 50 microliters per minute, while the flow rate of calibration fluid through the second flow line 40 toward the adapter 28 is about 100 microliters per minute. Consequently, calibration fluid flows into the fluid exchange region 55 from the second passage 56 at twice the flow rate that the calibration fluid is drawn from the fluid exchange region 55 through the first passage 54.
  • the first check valve 44 is opened to allow fluid to travel through the first flow line 38 toward the pump 34, while the second check valve 46 is closed to prevent flow from reaching the pump 34.
  • the calibration fluid from the source of calibration fluid 32 flows from the second flow line 40 into the second passage 56.
  • the second passage 56 conveys the calibration fluid to the fluid exchange region 55.
  • calibration fluid from the third portion 65 of the second passage 56 i.e., within the sheath concentrically about the first passage 54
  • Such a concentric configuration in combination with the two times flow rate provided by the second flow line 40, promotes the pump 34 to draw only the calibration fluid up the conduit 66 and into the first flow line 38.
  • Excess calibration fluid flows out the catheter sheath 24 and into the patient thereby preventing blood from entering the fluid exchange region 55.
  • the sensor 30 can be calibrated and kept free of blood protein attachment or blockage by clots.
  • the pinch valve 48 is used to close the second flow line 40 (as shown in Figure 9). By closing the second flow line 40, the flow of calibration fluid to the adapter 28 is stopped.
  • the pump 34 will soon evacuate the fluid exchange region 55 of its remaining volume of calibration fluid and cause a sample fluid (e.g., blood) to flow from the patient into the catheter sheath 24. From the catheter sheath 24, the blood travels through the first passage 54 into the first flow line 38.
  • the first flow line 38 carries the blood to the sensor 30.
  • a substantially calibrant free volume of sample fluid will be drawn into the sensor 30.
  • a measurement e.g., a lactate measurement
  • a pump such as a small volume syringe offers the advantage of increased control of flow rates through the first flow line 38.
  • a small volume syringe e.g., about 3 cubic centimeters (cc)
  • cc cubic centimeters
  • the syringe purge is accomplished by commanding the pump 34 (e.g., a syringe driven by a syringe driver) to reverse direction at a predetermined rate of travel (as shown in Figure 10).
  • the reverse flow in the first flow line 38 causes the second check valve 46 located along the third flow line 42 to open. Consequently, flow proceeds through the third flow line 42 and into the waste container 36 (e.g., a waste bag).
  • the waste container 36 e.g., a waste bag.
  • the second flow line 40 is preferably opened to allow calibration fluid to flow through the catheter 22 to inhibit clotting.
  • a large volume syringe in the range of 30 cc to 60 cc can be used if such use does not induce detrimental flow characteristics to the system.
  • the total volume of the syringe could be equal to the greatest anticipated waste volume for a given sensor life cycle, thus eliminating the need for the check valves 44 and 46 and for the waste container 36.
  • control unit 144 can be programmed to cause the sensor arrangement 20 to take fluid samples at predetermined time intervals. For example, samples can be taken every hour, or every fifteen minutes, or every five minutes. During the time periods between sampling, the sensor 30, is preferably bathed in calibration fluid.
  • the sensor arrangement 20 is particularly suited for use as a disposable ex vivo lactate monitor.
  • the sensor arrangement 20 can automatically, via the controller 144, sample lactate readings at predetermined intervals such as every hour, every fifteen minutes, or every five minutes. Current lactate readings can be displayed on a display unit. Furthermore, trends such as increases in lactate concentration, decreases in lactate concentration, and rates of lactate concentration change can be stored in memory associated with the controller 144. Such information can be used to provide a physician with a data such as a lactate history line or an average lactate reading for a particular patient on a given day.

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Claims (22)

  1. Eine Sensoranordnung (20) umfassend einen Katheter (22) einschließlich einer zur Einführung in einen Patienten anwendbaren Katheterhülle (24), eine Pumpe (34), einen Sensor (30) und einen Behälter (32) zum Beinhalten einer Kalibrierungsflüssigkeit, welche eine zur Kalibrierung des Sensors (30) anwendbare Kalibriersubstanz einschließt,
    dadurch charakterisiert, dass die Sensoranordnung (20) weiterhin
    ein mit der Katheterhülle (24) verbundenes Katheteransatzstück (26);
    einen mit dem Katheteransatzstück (26) verbundenen Adapter (28), welcher den ersten und zweiten Anschluss (100; 102) einschließt; wobei der Adapter (28) separate erste und zweite Wege festlegt (54; 56), wobei der erste Weg (54) sich von dem ersten Anschluss (100) bis zu einer inneren Region (50) der Katheterhülle (24) erstreckt und der zweite Weg (56) sich von dem zweiten Anschluss (102) bis zu einer inneren Region des Katheteransatzstücks (26) erstreckt;
    zwei Flussleitungen, wobei die erste Flussleitung (38) sich zwischen dem Adapter (28) und der Pumpe (34) erstreckt und die erste Flussteitung (38) mit dem ersten Anschluss (100) des Adapters (28) verbunden ist, und die zweite Flussleitung (40) sich zwischen dem Adapter (28) und dem Behälter (32) erstreckt und die zweite Flussleitung (40) mit dem zweiten Anschluss (102) des Adapters (28) verbunden ist;
    und den Sensor (30), weicher entlang der ersten Flussleitung (38) positioniert ist
    umfasst.
  2. Die Sensoranordnung (20) nach Anspruch 1, worin der Sensor (30) einen Lactat-Sensor umfasst.
  3. Die Sensoranordnung (20) nach Anspruch 1, worin der Behälter (32) einen Beutel für intravenöse Infusionen umfasst.
  4. Die Sensoranordnung (20) nach Anspruch 1, worin die Pumpe (34) eine Spritze umfasst.
  5. Die Sensoranordnung (20) nach Anspruch 1, worin der Adapter (28) einen Einschubbereich (58) einschließt, welcher in das Katheteransatzstück (26) passt, worin der erste Weg (54) durch eine Röhre (66) definiert ist, die sich durch den Einschubbereich (58) erstreckt und worin die Röhre (66) einen Endbereich (108) besitzt, der sich nach außen aus dem Einschubbereich (58) und in die Katheterhülle (24) erstreckt.
  6. Die Sensoranordnung (20) nach Anspruch 5, worin der Einschubbereich (58) einen Bereich mit der Form eines abgestumpften Kegels (76) besitzt, wobei der Bereich mit der Form eines abgestumpften Kegels (76) ein erstes Ende (70) mit einem kleineren Durchmesser und ein zweites Ende (72) mit einem größeren Durchmesser besitzt und worin der Endbereich der Röhre (66) axial aus dem ersten Ende (70) herausragt.
  7. Die Sensoranordnung (20) nach Anspruch 5, worin der Einschubbereich (58) des Adapters (28) zumindest einen Teil des zweiten Weges (56) definiert.
  8. Die Sensoranordnung (20) nach Anspruch 7, worin der Teil des zweiten Weges (56), der durch den Einschubbereich (58) des Adapters (28) definiert wird, zumindest teilweise die Röhre (66) umgibt, welche den ersten Weg (54) definiert.
  9. Die Sensoranordnung (20) nach Anspruch 7, worin der Teil des zweiten Weges (56), der durch den Einschubbereich (58) des Adapters (28) definiert wird, die Röhre (66), welche den ersten Weg (54) definiert, konzentrisch umgibt.
  10. Die Sensoranordnung (20) nach Anspruch 1, worin der erste Weg (54) zumindest teilweise durch eine Röhre (66) definiert ist, die sich in die Katheterhülle (24) hinein erstreckt und angrenzend an eine distale Spitze (57) der Katheterhülle (24) endet.
  11. Die Sensoranordnung (20) nach Anspruch 10, worin die Röhre (66) an einer Stelle endet, welche sich nicht weiter als 1 Zentimeter von der distalen Spitze.(57) der Katheterhülle (24) entfernt befindet.
  12. Die Sensoranordnung (20) nach Anspruch 10, worin die Röhre (66) an einer Stelle endet, welche sich nicht weiter als 1 Millimeter von der distalen Spitze (57) der Katheterhülle (24) entfernt befindet.
  13. Eine Sensoranordnung (20) umfassend
    einen Katheter (22) einschließlich einer zur Einführung in einen Patienten anwendbaren Katheterhülle (24), einen Sensor (30), eine Pumpe (34) und eine Quelle von Kalibrierungsflüssigkeit (32), welche zur Kalibrierung des Sensors (30) anwendbar ist,
    dadurch charakterisiert, dass die Sensoranordnung (20) weiterhin
    eine erste Struktur, die einen ersten Flussweg (54) definiert, welcher sich innerhalb der Katheterhülle (24) ausdehnt und innerhalb einer inneren Region (50) der Katheterhülle (24) endet;
    eine zweite Struktur, die einen zweiten Flussweg (56) definiert, welcher von dem ersten Flussweg (54) getrennt ist, wobei der zweite Flussweg (56) innerhalb der inneren Region (50) der Katheterhülle (24) endet
    umfasst;
    wobei der Sensor (30) in Fluidverbindung mit dem ersten Flussweg (54) positioniert ist;
    die Quelle der Kalibrierungsflüssigkeit (32) in Fluidverbindung mit dem zweiten Flussweg (56) ist, wobei die Quelle der Kalibrierungsflüssigkeit (32) die Kalibrierungsflüssigkeit einschließt, welche durch den zweiten Flussweg (56) der inneren Region (50) der Katheterhülle (24) zugeführt wird; und
    die Pumpe (34) in Fluidverbindung mit dem ersten Flussweg (54) ist, wobei die Pumpe (34) anwendbar ist, um eine Flüssigkeit von der inneren Region (50) der Katheterhülle (24) zu dem Sensor (30) zu ziehen.
  14. Die Sensoranordnung (20) nach Anspruch 13, worin die erste Struktur eine Röhre (66) einschließt, die in die Katheterhülle (24) eingeführt ist, wobei die Röhre (66) zumindest teilweise den ersten Flussweg (54) definiert, und ein Ende der Röhre (66) innerhalb der Katheterhülle (24) an einer Stelle positioniert ist, welche an eine distale Spitze (57) des Katheters angrenzt.
  15. Die Sensoranordnung (20) nach Anspruch 14, worin der zweite Flussweg (56) zumindest teilweise zwischen der Röhre (66) und der Katheterhülle (24) definiert ist.
  16. Die Sensoranordnung (20) nach Anspruch 14, worin zumindest ein Teil des zweiten Weges (56) die Röhre (66) innerhalb der Katheterhülle (24) konzentrisch umgibt.
  17. Ein Adapter (28) zur Verwendung mit einem Katheter (22) einschließlich einer Katheterhülle (24), welche mit einem Katheteransatzstück (26) verbunden ist, wobei die Katheterhülle (24) zur Einführung in einen Patienten anwendbar ist, und der Adapter (28) gekennzeichnet ist durch
    einen Adapterkörper (28), der den ersten und zweiten Anschluss (100; 102) definiert, welche zum Anschluss an medizinische Schläuche anwendbar sind;
    Ein Verbindungsstück (60), welches zur Befestigung des Adapterkörpers (28) mit dem Ansatzstück (26) anwendbar ist;
    Eine Röhre (66), welche sich von dem ersten Anschluss (100) durch den Adapterkörper (28) ausdehnt, wobei die Röhre (66) einen Endbereich (108) einschließt, der aus dem Adapterkörper (28) herausragt, und der Endbereich (108) so angeordnet und gestaltet ist, dass er in eine innere Region (50) der Katheterhülle (24) passt, wenn der Adapterkörper (28) mit dem Katheteransatzstück (26) verbunden ist; und
    Eine Struktur, welche einen von der Röhre (66) getrennten Weg (112,- 78) definiert, der sich von dem zweiten Anschluss (102) durch den Adapterkörper (28) ausdehnt, wobei der Weg (56) so angeordnet und gestaltet ist, dass eine Fluidverbindung zwischen dem zweiten Anschluss (102) und einer inneren Region (77) des Katheteransatzstücks (26) gewährleistet ist, wenn der Adapterkörper (28) mit dem Katheteransatzstück (26) verbunden ist.
  18. Der Adapter (28) nach Anspruch 17, worin der Adapter (28) einen Einschubbereich (58) einschließt, welcher von der Größe und Form in das Katheteransatzstück (26) passt, und worin der Endbereich (108) der Röhre (66) sich aus dem Einschubbereich (58) heraus erstreckt.
  19. Der Adapter (28) nach Anspruch 18, worin der Einschubbereich (58) einen Bereich einschließt, welcher hauptsächlich die Form eines abgestumpften Kegels besitzt (76), wobei der Bereich mit der Form eines abgestumpften Kegels (76) ein erstes Ende (70) mit einem kleinen Durchmesser und ein zweites Ende (72) mit einem großen Durchmesser besitzt und worin der Endbereich (108) der Röhre (66) axial aus dem ersten Ende (70) herausragt.
  20. Der Adapter (28) nach Anspruch 18, worin der Einschubbereich (58) des Adapters (28) zumindest einen Teil des Weges (56) definiert.
  21. Der Adapter (28) nach Anspruch 20, worin der Teil des zweiten Weges (56), welcher durch den Einschubbereich (58) des Adapters (28) definiert ist, zumindest teilweise die Röhre (66) innerhalb des Einschubbereichs (58) umgibt.
  22. Der Adapter (28) nach Anspruch 20, worin der Teil des zweiten Weges (56), welcher durch den Einschubbereich (58) des Adapters definiert ist, die Röhre (66) innerhalb des Einschubbereichs (58) konzentrisch umgibt.
EP99964283A 1998-12-16 1999-12-16 System zur messung eines bioanalyts wie laktat Expired - Lifetime EP1139860B1 (de)

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US212557 1998-12-16
US09/212,557 US6128519A (en) 1998-12-16 1998-12-16 System and method for measuring a bioanalyte such as lactate
PCT/US1999/030122 WO2000035340A1 (en) 1998-12-16 1999-12-16 A system and method for measuring a bioanalyte such as lactate

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EP1139860A1 (de) 2001-10-10
JP4475816B2 (ja) 2010-06-09
US6128519A (en) 2000-10-03
JP2002532124A (ja) 2002-10-02
DE69918859D1 (de) 2004-08-26
DE69918859T2 (de) 2005-08-11
WO2000035340A1 (en) 2000-06-22
ATE271347T1 (de) 2004-08-15

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